Aim: To investigate the influence of different stimulators on cytokines secretion of tumor-draining lymph node (TDLN) cells and study antitumor effects and mechanism of TDLN cells.
Methods: IL-12 p70, IFN-gamma, TNF-alpha and NO which were secreted by TDLN cells induced by different stimulators (IL-2 group, IL-2+autologous tumor antigen group, IL-2+GM-CSF+IL-4+autologous tumor antigen group and IL-2+GM-CSF+IL-4+LPS group) were detected by ELISA and Griess after TDLN cells were stimulated for 7, 14 and 21 d.
Results: The rate of CD83(+) cells of TDLN cells induced by IL-2+GM-CSF+IL-4+autologous tumor antigen and IL-2+GM-CSF+IL-4+LPS was significantly increased. The TDLN cells in the two groups secreted much more IL-12 p70, IFN-gamma and TNF-alpha than IL-2 group and IL-2+autologous tumor antigen group. The TDLN cells stimulated by IL-2+GM-CSF+IL-4+LPS secreted significantly more NO than the other three groups. TDLN cells in each group secreted IL-12 p70, IFN-gamma and NO at the highest level after TDLN cells were stimulated for 14 d.
Conclusion: Different stimulators can make TDLN cells produce different number of CD83(+) cells (DC), which gives TDLN cells different antitumor activity.
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bioRxiv
December 2024
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood.
View Article and Find Full Text PDFBr J Cancer
January 2025
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling.
Methods: We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM.
Cancer Cell
December 2024
Genome Institute of Singapore, Agency for Science, Technology, and Research (A(∗)STAR), 60 Biopolis Street, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore. Electronic address:
Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities, Shandong Lung Cancer Institute, 16766 Jingshi Road, Jinan, 250014, P. R. China.
For medically inoperable non-small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains a concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits tumor recurrence by CD8 central memory T (T)-like cell-dependent antitumor immune responses within the tumor-draining lymph nodes (TdLN).
View Article and Find Full Text PDFFront Immunol
October 2024
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
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